Changes in fat distribution are increasingly recognized in HIV-infected patients, in association with dyslipidemia and insulin resistance. Abdominal visceral fat is markedly increased, whereas abdominal and peripheral subcutaneous fat are significantly reduced in patients with HIV-related lipodystrophy. Recent studies demonstrate reduced growth hormone (GH) levels in patients with HIV lipodystrophy compared to age and BMI-matched healthy control subjects. More specfcally, subjects with HIV lipodystrophy demonstrate reduced mean GH concentrations, basal GH concentrations, and GH pulse amplitude, but normal GH pulse frequency and IGF-1 levels. Increased visceral fat is the single best predictor of reduced GH secretion in HIV lipodystrophy. The abnormal pattern of GH secretion seen in HIV lipodystrophy may result either from increased somatostatin tone or reduced growth hormone releasing hormone (GHRH) or direct pituitary effects. In addition, increased free fatty acid levels resulting from visceral adiposity may contribute to abnormal GH secretion in this population. In the proposed grant, we will investigate the pathophysiology of the altered growth hormone pattern found in individuals with HIV lipodystrophy and determine the potential role of increased endogenous somatostatin tone and/or reduced hypothalamic GHRH in mediating altered GH dynamics in this population. Furthermore, we will investigate the potential role of increased free fatty acids in mediating abnormal GH secretion in HIV lipodystrophy.